Tissues 4- Extracellular Matrix Biology II Flashcards
Describe structure(5) and function (2) of lamins
Structure:
Contains of 3 chains - one each of an a, b and g chain
Forms a CROSS-SHAPED MOLECULE
Very LARGE
Multi-adhesive
At the N terminus all the chains have Globular Regions.
Function:
Interact with cell surface receptors
Can self-associate as part of the basement membrane matrix and can interact with other ECM components
Notes:
Found in ALL basement membranes
Different regions on the laminin have different binding capacities.
What is Congenital Muscular Dystrophy
Caused by Absence of a2 in laminin 2
Hypotonia
Generalised weakness
Deformities of the joints
Describe structure(4) and function (4) of Fibronectins
Structure:
LARGE
Multi-adhesive
Two units are linked by a disulphide bridge
Can exist as insoluble fibrillar matrix or soluble plasma protein
Function:
Regulating cell adhesion and migration in embryogenesis and tissue repair
Wound healing (promotes blood clotting)
Different regions interacting with different components.
Capable of interacting with cell surface receptors and other matrix molecules
Notes:
Only derived from ONE GENE - different forms of fibronectin come from different types of mRNA splicing.
NO KNOWN MUTATIONS IN HUMANS - suggests that it is essential for life
NOT found in basal membranes but is a major connective tissue glycoprotein.
Forms a mechanical continuum with the actin cytoskeleton of many cell types
What is intergrin
Fibronectin is linked to the actin cytoskeleton via integrins
Fibronectin —- Integrin —- Actin
The extracellular region of the integrin links with fibronectin and the intracellular region links with actin.
Integrin binds to the RGD sequence
What do Proteoglycans consist of
Consists of a CORE PROTEIN onto which one or more GLYCOSAMINOGLYCAN (GAG) CHAINS are covalently attached.
GAG chains are long, unbranched sugars consisting of a REPEATING DISACCHARIDE
GAGs occupy a large volume relative to their mass.
GAGs form hydrated gels which can be very resistant to compression
The 4 families proteoglycans are catergorised into
Basement Membrane e.g. perlecan
Aggregating (interact with hyaluron) e.g. aggrecan
Small Leucine-Rich e.g. decorin
Cell Surface e.g. syndecans 1-4
Describe glycosaminoglycan chains and what are the 4 main groups
One of the two sugars in the repeating disaccharide is always an amino sugar.
Highly Negatively Charged - many GAGs are sulfated or carboxylated
GAG chains and the core protein are linked via a LINK TETRASACCHARIDE
Four main groups of GAG chains: Hyaluron Chondroitin Sulfate/Dermatan Sulfate Heparan Sulfate Keratan Sulfate
what is Hyaluron
Unique- Has no core protein…. it only has a carbohydrate chain
Synthesised in the cell surface
Unsulfated
A single long chain has up to 25,000 repeat disaccharides
What are GAG chains and the core protien linked via
LINK TETRASACCHARIDE
What is decorin
A Small proteoglycan
Binds to collagen fibres
Regulates collagen fibre size and arrangement-
without it= fragile skin and reduced tensile strength
What is hylaine cartilage
Most abundant type of cartilage
Rich in AGGRECAN
Cushions the ends of long bones
Aggrecan and Cartilage Function
The GAGs of aggrecan are highly sulfated and there are many carboxyl groups - this makes it HIGHLY NEGATIVELY CHARGED
The high negative charge attracts cations that are osmotically active (e.g. Sodium)
So a large amount of WATER is retained by this highly negatively charged environment
It forms a gel - if you put pressure on the structure, the water gets squeezed out and if the compressive load is removed - the water returns.
This is how aggrecan can withstand compressive forces.
Describe Osteoarthritis
Characterised by loss of extracellular matrix
Can affect any joint but often affects fingers and knees
What happens:
There is a loss of cartilage, inflammation and new bone formation.
This can lead to joint stiffness and the rubbing of bone against bone.
Aggrecan gets degraded and the fragments get lost in the synovial fluid
What are Fibrotic Disorders
when there is too much extracellular matrix - normal tissue gets replaced by fibrotic tissue (normal tissue is replaced with collagen)
